This proposal aims to identify unique microRNA signatures that associated with the oral squamous cell carcinoma (SCC) initiation and progression. The attaining of these molecular signatures will lead to a set of novel biomarkers for the early detection of oral SCC. In addition, the microRNA-mRNA regulatory modules will be explored. The strategic integration of our observations at microRNA and mRNA levels will advance the overall understanding of this disease process at system biology level. An additional goal of this proposal is to establish an animal model that permits high throughput genomic analysis of the oral SCC disease process. Most of the early studies utilized a hamster model to study oral cancer. Due to the lack of in-depth knowledge on hamster genome, only limited genomic analyses can be performed on this model. In this study, we will establish a tobacco carcinogen induced oral cancer model in mice. Our preliminary results demonstrated the feasibility of this mouse model. This will enable us to perform genome-wide genomic analysis and lead to better understanding of the initiation and progression of this disease, as well as the identification of biomarkers for the early detection of oral cancer. Two specific aims were proposed to accomplish these objectives: The Specific Aim 1 is to establish a mouse oral cancer model induced with physiological tobacco carcinogen. This mouse model will provide us with unique opportunity to study alteration in microRNA (as well as other genome-wide studies) during the course of oral carcinogenesis. The Specific Aim 2 is to identify microRNA signatures and their correlation with mRNA expression patterns for oral cancer initiation and progression. Statistical and bioinformatic approaches will be used to identify potential markers and their classification power will be evaluated. The microRNA-mRNA regulatory modules will also be identified and evaluated.